Phosphonodithioylacetyl phenyl aminoacid ethyl esters

ABSTRACT

Novel compounds having the formula ##STR1## wherein R is lower alkyl having 1 to 6 carbon atoms, have shown utility as insecticides and miticides.

BACKGROUND OF THE INVENTION

This invention relates to novel compounds having the structural formula##STR2## wherein R is lower alkyl having from 1 to 6 carbon atoms andpreferably 2 to 4 carbon atoms. Examples of lower alkyl groups aremethyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, i-butyl, andn-amyl.

This invention also relates to a method of controlling or combattinginsects or mites by applying an insecticidally or miticidally effectiveamount of a compound as defined herein to the insect or the habitatthereof, or to a locus at which insecticidal or miticidal protection isdesired.

This invention also relates to insecticidal or miticidal compositions ofmatter comprising an insecticidally or miticidally effective amount of acompound as defined herein with an insecticidally or miticidallysuitable diluent or carrier.

DESCRIPTION OF THE INVENTION

The novel compounds that are useful in the practice of this inventionare phosphonodithioylacetyl phenyl aminoacid ethyl esters having thefollowing structural formula ##STR3## wherein R is lower alkyl havingfrom 1 to 6 carbon atoms and preferably 2 to 4 carbon atoms.

These compounds are useful as insecticides and miticides alone or whencompounded with carriers or other active ingredients.

The novel compounds of this invention can be prepared by the followinggeneral procedure:

1. Preparation of an aminoacid ester

An aminoacid is suspended in an excess of the alcohol from which theester is to be prepared and gaseous hydrogen chloride is passed into themixture at 25°-65° C. An excess of hydrogen chloride of from 3 to 4-5times the molar amount of aminoacid is used. The product, the aminoacidester hydrochloride, can be used directly in step 2 or may optionally beconverted to the free ester of reaction with ammonium hydroxide.

2. Preparation of a chloroacetylaminoacid ester

The ester prepared in step 1 is reacted with chloroacetylchloride at atemperature of from about -10° to +10° C. in a suitable solvent in thepresence of a suitable base to produce the correspondingchloroacetylaminoacid ester. Solvents useful in this reaction includewater, dichloromethane, and dichloroethane. Suitable bases includesodium bicarbonate, sodium carbonate, potassium carbonate, and sodiumhydroxide. If the aminoacid is used in the form of its hydrochloride, atwo-fold excess of base must be used.

3. Preparation of alkyl-O-alkylphosphonodithioylaminoacid ester

The chloroacetylaminoacid ester prepared in step 2 is reacted with analkyl-O-alkyldithiophosphate or salt thereof at a temperature below 25°C. in a suitable solvent in the presence of a suitable base to producethe corresponding alkyl-O-alkylphosphonodithioylaminoacid ester.Suitable solvents include tetrahydrofuran, dioxane, dichloromethane anddichloroethane. Suitable bases include triethylamine and pyridine. Whenthe salt form of the dithiophosphate is used in the reaction the organicbase is not required.

The following examples demonstrate preparation and testing of selectedcompounds of this invention.

EXAMPLE

Preparation of D-ethyl-O-ethylphosphonodithioylacetyl α-phenylglycine,ethyl ester

In a reaction flask, 3.8 grams (g) (0.015 ml) ofD-chloroacetyl-α-phenylglycine ethyl ester and 2.9 g (0.017 mole) ofethyl-O-ethyldithiophosphate in 35 milliliters (ml) tetrahydrofuran weremixed and cooled to 15° C. in an ice bath. Triethylamine (1.7 g, 0.01mole) was added at a temperature below 25° C. with cooling. The pH wasadjusted to about 7.5 with additional triethylamine and the mixture wasstirred for four hours at room temperature. The solvent was then removedunder vacuum and the residue was taken up in 75 ml of benzene and washedwith two 100 ml portions of dilute salt solution. The benzene solutionwas then dried over magnesium sulfate, filtered and evaporated to give5.1 g (87.9% yield) of an amber viscous liquid having an n_(D) ³⁰=1.5523. The product was identified by nuclear magnetic resonance (NMR)spectroscopy as the title compound.

The following is a table of certain selected compounds that are usefulin the practice of this invention. These compounds are preparableaccording to the general and specific procedure described herein.Compound numbers are assigned to each compound and are used throughoutthe remainder of this application.

                  TABLE I                                                         ______________________________________                                         ##STR4##                                                                     Compound No.     R         n.sub.D.sup.30                                     ______________________________________                                        1                C.sub.2 H.sub.5                                                                         1.5523                                             2                C.sub.3 H.sub.7i                                                                        1.5461                                             3                C.sub.4 H.sub.9i                                                                        1.5444                                             ______________________________________                                    

The structures of these compounds were confirmed by infrared (IR) and/ornuclear magnetic resonance (NMR) spectral analyses.

Insecticidal Evaluation

The compounds in the above Table I were tested for insecticidal acitvityagainst the following insects:

Housefly [Musca domestica (Linn.)]

German Cockroach [Blatella germanica (Linn.)]

Lygus Bug [Lygus hesperus (Knight)]

Black Bean Aphid [Aphis fabae (Scop.)]

Green Peach Aphid [Myzus persicae (Sulzer)]

Saltmarsh Caterpillar [Estigmene acrea (Drury)]

Tobacco Budworm [Heliothis virescens (Fabricius)]

Cabbage Looper [Trichoplusia ni (Hubner)]

Southern House Mosquito [Culex pipiens quinquefasciatus (Say)]

The following testing procedures were used for this evaluation.

Housefly [Musca domestica]:

Test compounds were diluted in acetone and aliquots pipetted onto thebottom of 55×15 mm aluminum dishes. To insure even spreading of thechemical on the bottom of the dishes, 1 ml of acetone containing 0.02%peanut oil was also added to each dish. After all solvents hadevaporated, the dishes were placed in circular cardboard cagescontaining 25 female houseflies, one to two days old. The cages werecovered on the bottom with cellophane and on the top with tulle netting,and each contained a sugar-water saturated cotton plug for maintenanceof the flies. Mortality was recorded after 48 hours. Test levels rangedfrom 100 ug/25 female houseflies down to that at which approximately 50%mortality occurred. The LD-50 values are expressed below in Table IIunder the heading "HF", in terms of ug of the test compound per 25female houseflies.

German Cockroach [Blatella germanica (Linn.)]:

Test compounds were diluted in a 50-50 acetone-water solution. Two cc ofthe solution was sprayed through a hand spray gun into circularcardboard cages containing 10 one-month old German cockroach nymphs. Thetest cages were covered on the bottom with cellophane and on the topwith tulle netting. Percent mortality was recorded 4 days later. Testconcentrations ranged from 0.1% down to that at which approximately 50%mortality occurred. LD-50 values are expressed below in Table II underthe heading "GR" in terms of percent of the test compound in the sprayedsolution.

Lygus Bug [Lygus hesperus (Knight)]:

Test compounds were diluted in a 50-50 acetone-water solution. Two cc ofthe solution were sprayed through a hand spray gun into circularcardboard cages containing 1 green bean pod and 10 adult lygus bugs. Thetest cages were covered on the bottom with cellophane and on the topwith tulle netting. Percent mortality was recorded 48 hours later. Testconcentrations ranged from 0.05% down to that at which approximately 50%mortality occurred. LD-50 values are expressed below in Table II underthe heading "LB" in terms of percent of the test compound in the sprayedsolution.

Black Bean Aphid [Aphis fabae (Scop.)]:

Nasturtium plants (Tropaeolum sp.) approximately 5 cm tall, weretransplanted into sandy loam soil in 3-inch clay pots and infested with25-50 black bean aphids of mixed ages. Twenty-four hours later they weresprayed to the point of runoff with 50-50 acetone-water solutions of thetest chemicals. Treated plants were held in the greenhouse and mortalitywas recorded after 48 hours. Test concentrations ranged from 0.05% downto that at which 50% mortality occurred. LD-50 values are expressedbelow in Table II under the heading "BA" in terms of percent of the testcompound in the sprayed solution.

Green Peach Aphid [Myzus persicae (Sulzer)]:

Radish plants (Rhaphanus sativus), approximately 2 cm tall, weretransplanted into sandy loam soil in 3-inch clay pots and infested with25-50 green peach aphids of mixed ages. Twenty-four hours later theywere sprayed to the point of run-off with 50-50 acetone-water solutionsof the test chemicals. Treated plants were held in the greenhouse andmortality was recorded after 48 hours. Test concentrations ranged from0.05% down to that at which 50% mortality occurred. LD-50 values areexpressed below in Table II under the heading "GPA" in terms of percentof the test compound in the sprayed solution.

Saltmarsh Caterpillar [Estigmene acrea (Drury)]:

Test compounds were diluted in a 50-50 acetone-water solution. Sectionsof curly dock (Rumex crispus) leaves, approximately 1×1.5 inches, wereimmersed in the test solution for 2-3 seconds and placed on a wirescreen to dry. The dried leaves were placed in petri dishes containing amoistened piece of filter paper and infested with 5 second-instarsaltmarsh larvae. Mortality of the larvae was recorded 48 hours later,and a piece of synthetic medium was added to dishes containingsurvivors. These were then held for 5 additional days to observe for anydelayed effects of the test chemicals.

Test concentrations ranged from 0.05% down to that at whichapproximately 50% mortality occurred. LD-50 values are expressed belowin Table II under the heading "SMC" in terms of percent of the testcompound in the solution.

Cabbage Looper [Trichoplusia ni (Hubner)]:

Test compounds were diluted in a 50-50 acetone-water solution.Cotyledons of hyzini squash (Calabacita abobrinha), approximately 1×1.5inches, were immersed in the test solutions for 2-3 seconds and placedon a wire screen to dry. The dried leaves were placed in petri dishescontaining a moistened piece of filter paper and infested with fivesecond-instar cabbage looper larvae. Mortality of the larvae wasrecorded 48 hours later, and a piece of synthetic media added to dishescontaining survivors. These were then held for five additional days toobserve for any delayed effects of the test chemicals.

Test concentrations ranged from 0.05% to that at which approximately 50%mortality occurred. LD-50 values are expressed below in Table II underthe heading "CL" in terms of percent of the test compound in thissolution.

Tobacco budworm [Heliothis virescens (Fabricius)]:

Test compounds were diluted in a 50-50 acetone-water solution. Sectionsof Romanine lettuce (Latuca sativa) leaves, approximately 1×1.5 inches,were immersed in the test solutions for 2-3 seconds and placed on a wirescreen to dry. The dried leaves were placed in petri dishes containing amoistened piece of filter paper and infested with five second-instartobacco budworm larvae. Mortality of the larvae was recorded 48 hourslater, and a piece of synthetic media added to dishes containingsurvivors. These were then held for five additional days to observe forany delayed effects of the test chemicals.

Test concentrations ranged from 0.05% to that at which approximately 50%mortality occurred. LD-50 values are expressed below in Table II underthe heading "TBW" in terms of percent of the test compound in thesolution.

Southern House Mosquito Larvae [Culex pipiens quinquefasciatus (Say)]:

Insecticidal activity was determined using third instar larvae of themosquito Culex pipiens quinquefasciatus. Ten larvae were placed in a sixounce paper cup containing 100 milliliters of an aqueous solution of thetest chemical. The treated larvae were stored at 70° F., and 48 hourslater the mortality was recorded. Test concentrations ranged from 1.0ppm down to that at which approximately 50% mortality occurred. LD-50values are expressed below in Table II under the heading "MOS" in termsof parts per million (ppm) of the test compound in the solution.

Acaricidal Evaluation Test

The two-spotted mite (2SM), Tetranychus urticae (Koch), was employed intests for miticides. The test procedure was as follows:

Pinto bean plants (Phaseolus sp.) approximately 10 cm tall, weretransplanted into sandy loam soil in 3-inch clay pots and thoroughlyinfested with two-spotted mites of mixed ages and sexes. Twenty-fourhours later the infested plants were inverted and dipped for 2-3 secondsin 50-50 acetone-water solutions of the test chemicals. Treated plantswere held in the greenhouse, and 7 days later mortality was determinedfor both adult mites and the nymphs hatching from eggs which were on theplants at the time of treatment. Test concentrations ranged from 0.05%down to that at which 50% mortality occurred. LD-50 values are expressedbelow in Table II under the headings "2SM-PE" (i.e., post-embryonic) and"2SM-Eggs", in terms of percent concentrations of the test compound inthe solution.

                                      TABLE II                                    __________________________________________________________________________    Comp.                                                                             HF, GR LB  BA GPA                                                                              SMC TBW CL  MOS PE  EGGS                                 No. ug  %  %   %  %  %   %   %   ppm %   &                                    __________________________________________________________________________    1   >100                                                                              >0.1                                                                             >0.05                                                                             0.008                                                                            0.008                                                                             0.03                                                                             >0.05                                                                             >0.05                                                                             >1   0.05                                                                             <0.05                                2    100                                                                              -- --  0.008                                                                            0.03                                                                             --  >0.05                                                                             --  >1  <0.05                                                                             <0.05                                3    100                                                                              >0.1                                                                             >0.05                                                                             0.005                                                                            0.002                                                                            <0.01                                                                             >0.05                                                                             >0.05                                                                             0.8 >0.05                                                                             >0.05                                __________________________________________________________________________

In practice, a pure compound can be used as an insecticide. However, ingeneral, the compounds are first formulated with one or more inertcarriers or diluents suitable for insecticidal use, before beingapplied.

The compositions or formulations, including a compound as describedherein, may take and be used in any one of a number of solid or liquidforms. Examples of solid forms are dusts, granules, tablets, powders,and the like. Examples of liquid forms are emulsions, solutions,suspensions, emulsifiable concentrates, flowables, and pastes. Suchcompositions may contain, in addition to the active compound orcompounds, various carriers or diluents; surface active agents (wettingagents, dispersing agents and/or emulsifying agents); solvents (water ororganic solvents such as aromatic solvents or chlorinated aliphaticsolvents); adhesives; thickeners; binders; antifoaming agents; and othersubstances as mentioned herein. Solid carriers or diluents included insuch compositions or formulations may include, for example, groundnatural minerals such as kaolins, alumina, calcium carbonate, silica,kieselguhr, clay, etc.; ground synthetic minerals such as varioussilicates and aluminosilicates and ground vegetable products such asbark, cornmeal, sawdust, cellulose powder and the like.

To manufacture solid compositions, the active substances are mixed withsolid carriers or diluents such as those mentioned above and the mixtureis ground to the appropriate size. Granules can be manufactured bydissolving an active compound in an organic solvent and applying themixture, for example, by atomization, onto an absorptive granulatedinert material, such as silica. Adhesives may be utilized to assist inthe incorporation of the compound onto the solid particles.

Wettable powders, flowables and pastes are obtained by mixing andgrinding an active compound with one or more dispersing agents and/orsolid carriers or diluents. Also included may be wetting agents and/ordispersing agents, for example, lignins, methyl cellulose,naphthalenesulfonic acid derivatives, fatty alcohol sulfates and varioustypes of alkali and alkaline earth metal salts of fatty acids.

Emulsifiable concentrates are generally obtained by dissolving theactive compound in an organic solvent, for example, butanol,cyclohexanone, xylenes, or higher boiling aromatic hydrocarbons with anemulsifying agent. To obtain suspensions or emulsions in water, wettingagents are also added.

It is possible to use highly concentrated liquid compositions containingup to about 95% by weight of the active compound, or even the 100%active compound alone, when applying the compound in the form of afinely divided liquid by use of various atomizing equipment, for exampleby airplane crop spraying techniques. For other purposes, however, thevarious types of compositions which can be utilized for these compoundswill contain varying amounts of the compound according to the type ofcomposition and the intended use.

In general, compositions may contain from 0.1 to 95% of the activecompound, more preferably from 0.5 to 90%. Some typical compositionswill contain an active compound as follows: wettable powders, flowablesand pastes,--20 to 90% active compound; oil suspensions, emulsions,solutions and emulsifiable concentrates--5 to 90% active compound;aqueous suspensions--10 to 50% active compound; dusts and powders--1 to25% active compound; granules and pellets--1 to 20% active compound.

The rate of application of the active compound to a locus to becontrolled will depend on the nature of the insects to be controlled andwill vary from about 0.05 to about 50 pounds per acre (about 0.06 toabout 56 kg/ha).

In addition to the active compound and the various agents utilized inpreparing compositions and formulations mentioned above, suchcompositions may also contain one or more other active compounds of thetype mentioned herein as well as other active pesticidal agents, such asherbicides, fungicides, insecticides, acaricides, nematocides,bactericides, and plant growth regulators. Such compositions may alsocontain soil disinfectants or fumigants and may further containfertilizers, thus making it possible to provide multi-purposecompositions containing one or more of the compounds described herein aswell as, optionally, other pesticides and also fertilizers, all intendedand formulated for use at the same locus.

Control of insect pests is accomplished by applying a compositioncontaining an insecticidally effective amount of an active compound asdescribed herein, to the insect, to a locus at which insecticidalcontrol is desired, or to food sources (including seeds) on which theinsects feed. For use in the last mentioned manner, it is preferable toutilize a compound which is not volatile. Thus, control may be achievedby direct application of the active compounds to the insects andindirectly by application of the compounds to a locus to be protected(such as crop lands, grass ranges, and forests), to a source of food forinsects or to other insect habitats (for example, breeding or swarmingareas). The rates of application of the active compound, and theconcentration applied, will vary according to whether the compound orcomposition is being directly applied to the insect or indirectly, to alocus, food or habitat. In the latter case the rate of the application,depending on the nature of the insect or insects to be controlled, andthe plant environment, will generally vary from about 0.01 to about 100pounds per acre (about 0.112 to about 1120 kg/ha.)

What is claimed is:
 1. A method for controlling insects comprisingapplying to the insects, the habitat thereof, or a locus whereprotection is desired, an insecticidally effective amount of a compoundhaving the formula ##STR5## wherein R is lower alkyl having from 1 to 6carbon atoms.
 2. The method of claim 1 wherein R is -C₂ H₅.
 3. Themethod of claim 1 wherein R is -C₃ H₇ -i.
 4. The method of claim 1wherein R is -C₄ H₉ -i.
 5. A compound having the structural formula##STR6## wherein R is lower alkyl having from 1 to 6 carbon atoms. 6.The compound of claim 5 wherein R is -C₂ H₅.
 7. The compound of claim 5wherein R is -C₃ H₇ -i.
 8. The compound of claim 5 wherein R is -C₄ H₉-i.
 9. A composition of matter comprising(a) an insecticidally effectiveamount of a compound having the structural formula ##STR7## wherein R islower alkyl having from 1 to 6 carbon atoms; and (b) an insecticidallysuitable inert carrier or diluent.
 10. The composition of claim 9wherein R is -C₂ H₅.
 11. The composition of claim 9 wherein R is -C₃ H₇-i.
 12. The composition of claim 9 wherein R is -C₄ H₉ -i.